Skip to main content

Advertisement

Log in

Histone Deacetylase Modifications by Probiotics in Colorectal Cancer

  • Review Article
  • Published:
Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

Abstract

Summary

It has been demonstrated that epigenetic modifications of histone (acetylation/deacetylation) participate in a critical role in cancer progression by the regulation of gene expression. Several processes could be regulated by deacetylation of histone and non-histone proteins such as apoptosis, proliferation, cell metabolism, differentiation, and DNA repair. Hence, histone deacetylase inhibitors (HDACis) are employed as a hopeful group of anti-cancer drugs that could inhibit tumor cell proliferation or apoptosis. The elimination of the acetylation marks that take place as an essential epigenetic change in cancer cells is associated to HDAC expression and activity. In this regard, it has been reported that class I HDACs have a vital role in the regulation of tumor cell proliferation.

Objectives

In this review, we discuss whether gut origin microorganisms could promote cancer or tumor resistance and explain mechanisms of these processes.

Conclusions

According to the enormous capacity of the metabolism of the intestine microbiota, bacteria are likely to convert nutrients and digestive compounds into metabolites that regulate epigenetic in cancer. The effect of the food is of interest on epigenetic changes in the intestinal mucosa and colonocytes, as misleading nucleotide methylation may be a prognostic marker for colorectal cancer (CRC). Since epigenetic changes are potentially reversible, they can serve as therapeutic targets for preventing CRC. However, various mechanisms have been identified in the field of prevention, treatment, and progression of cancer by probiotics, which include intestinal microbiota modulation, increased intestinal barrier function, degradation of potential carcinogens, protective effect on intestinal epithelial damage, and increased immune function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Eslami M, et al. Importance of probiotics in the prevention and treatment of colorectal cancer. J Cell Physiol. 2019.

  2. Bultman SJ. Interplay between diet, gut microbiota, epigenetic events, and colorectal cancer. Mol Nutri Food Res. 2017;61(1):1500902.

    Google Scholar 

  3. Vaissière T, Sawan C, Herceg Z. Epigenetic interplay between histone modifications and DNA methylation in gene silencing. Mutat Res/Reviews in Mutation Research. 2008;659(1-2):40–8.

    Google Scholar 

  4. Guerra A, et al. Relevance and challenges in modeling human gastric and small intestinal digestion. Trends biotechnol. 2012;30(11):591–600.

    CAS  PubMed  Google Scholar 

  5. Peterson LW, Artis D. Intestinal epithelial cells: regulators of barrier function and immune homeostasis. Nat Rev Immunol. 2014;14(3):141.

    CAS  PubMed  Google Scholar 

  6. McCracken VJ, Lorenz RG. The gastrointestinal ecosystem: a precarious alliance among epithelium, immunity and microbiota: Microreview. Cell Microbiol. 2001;3(1):1–11.

    CAS  PubMed  Google Scholar 

  7. Groh V, et al. Cell stress-regulated human major histocompatibility complex class I gene expressed in gastrointestinal epithelium. Proc Natl Acad Sc. 1996;93(22):12445–50.

    CAS  Google Scholar 

  8. Marks PA, et al. Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer. 2001;1(3):194.

    CAS  PubMed  Google Scholar 

  9. Marks PA, Richon VM, Rifkind RA. Histone deacetylase inhibitors: inducers of differentiation or apoptosis of transformed cells. J Natil Cancer Inst. 2000;92(15):1210–6.

    CAS  Google Scholar 

  10. Grunstein M. Histone acetylation in chromatin structure and transcription. Nature. 1997;389(6649):349.

    CAS  PubMed  Google Scholar 

  11. Wolffe AP. Histone Deacetylase--A Regulator of Transcription. Science. 1996;272(5260):371–2.

    CAS  PubMed  Google Scholar 

  12. Zentner GE, Henikoff S. Regulation of nucleosome dynamics by histone modifications. Nat Struct Mol Biol. 2013;20(3):259.

    CAS  PubMed  Google Scholar 

  13. Madrigal P, Krajewski P. Uncovering correlated variability in epigenomic datasets using the Karhunen-Loeve transform. BioData mining. 2015;8(1):20.

    PubMed  PubMed Central  Google Scholar 

  14. Spange S, et al. Acetylation of non-histone proteins modulates cellular signalling at multiple levels. Int J Biochem Cell Biol. 2009;41(1):185–98.

    CAS  PubMed  Google Scholar 

  15. Cheung P, Allis CD, Sassone-Corsi P. Signaling to chromatin through histone modifications. Cell. 2000;103(2):263–71.

    CAS  PubMed  Google Scholar 

  16. Winston F, Allis CD. The bromodomain: a chromatin-targeting module? Nat Struct Mol Biol. 1999;6(7):601.

    CAS  Google Scholar 

  17. Ng HH, Bird A. Histone deacetylases: silencers for hire. Trends Biochem Sci. 2000;25(3):121–6.

    CAS  PubMed  Google Scholar 

  18. Lusser A, Kölle D, Loidl P. Histone acetylation: lessons from the plant kingdom. Trends Plant Sci. 2001;6(2):59–65.

    CAS  PubMed  Google Scholar 

  19. Gregoretti I, Lee Y-M, Goodson HV. Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J Mol Biol. 2004;338(1):17–31.

    CAS  PubMed  Google Scholar 

  20. Glozak M, Seto E. Histone deacetylases and cancer. Oncogene. 2007;26(37):5420.

    CAS  PubMed  Google Scholar 

  21. Witt O, et al. HDAC family: What are the cancer relevant targets? Cancer Lett. 2009;277(1):8–21.

    CAS  PubMed  Google Scholar 

  22. Dokmanovic M, Clarke C, Marks PA. Histone deacetylase inhibitors: overview and perspectives. Mol Cancer Res. 2007;5(10):981–9.

    CAS  PubMed  Google Scholar 

  23. Minucci S, Pelicci PG. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer. 2006;6(1):38.

    CAS  PubMed  Google Scholar 

  24. Marks PA, Miller T, Richon VM. Histone deacetylases. Curr Opin Pharmacol. 2003;3(4):344–51.

    CAS  PubMed  Google Scholar 

  25. De Ruijter AJ, et al. Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J. 2003;370(3):737–49.

    PubMed  PubMed Central  Google Scholar 

  26. Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Discov. 2006;5(9):769.

    CAS  PubMed  Google Scholar 

  27. Glaser KB, et al. Gene expression profiling of multiple histone deacetylase (HDAC) inhibitors: defining a common gene set produced by HDAC inhibition in T24 and MDA carcinoma cell lines. Mol Cancer Ther. 2003;2(2):151–63.

    CAS  PubMed  Google Scholar 

  28. Gump JM, Thorburn A. Autophagy and apoptosis: what is the connection? Trends Cell Biol. 2011;21(7):387–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Eslami M, et al. Current information on the association of Helicobacter pylori with autophagy and gastric cancer. J Cell Physiol. 2019.

  30. Yousefi B, et al. Role of autophagy associated with Helicobacter pylori CagA and VacA toxins in gastric cancer. Koomesh. 2019;21(2):205–14.

    Google Scholar 

  31. West AC, Johnstone RW. New and emerging HDAC inhibitors for cancer treatment. J Clin Invest. 2014;124(1):30–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Sayers TJ. Targeting the extrinsic apoptosis signaling pathway for cancer therapy. Cancer Immunol Immunother. 2011;60(8):1173–80.

    CAS  PubMed  Google Scholar 

  33. Rahmani M, et al. Coadministration of histone deacetylase inhibitors and perifosine synergistically induces apoptosis in human leukemia cells through Akt and ERK1/2 inactivation and the generation of ceramide and reactive oxygen species. Cancer Res. 2005;65(6):2422–32.

    CAS  PubMed  Google Scholar 

  34. Yang X, Seto E. HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention. Oncogene. 2007;26(37):5310.

    CAS  PubMed  Google Scholar 

  35. Shin J, et al. The intestinal epithelial cell differentiation marker intestinal alkaline phosphatase (ALPi) is selectively induced by histone deacetylase inhibitors (HDACi) in colon cancer cells in a Kruppel-like factor 5 (KLF5)-dependent manner. J Biol Chem. 2014;289(36):25306–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Felekkis K, et al. microRNAs: a newly described class of encoded molecules that play a role in health and disease. Hippokratia. 2010;14(4):236.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Bandres E, et al. MicroRNAs as cancer players: potential clinical and biological effects. DNA Cell Biol. 2007;26(5):273–82.

    CAS  PubMed  Google Scholar 

  38. Zhu P, et al. Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis. Cancer Cell. 2004;5(5):455–63.

    CAS  PubMed  Google Scholar 

  39. Mao Q, et al. MicroRNA-455 suppresses the oncogenic function of HDAC2 in human colorectal cancer. Braz J Med Biol Res. 2017:50(6).

  40. De Palma M, Biziato D, Petrova TV. Microenvironmental regulation of tumour angiogenesis. Nat Rev Cancer. 2017;17(8):457.

    PubMed  Google Scholar 

  41. Chou C-W, et al. HDAC inhibition decreases the expression of EGFR in colorectal cancer cells. PloS one. 2011;6(3):e18087.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Buckley DL, et al. Targeting the von Hippel–Lindau E3 ubiquitin ligase using small molecules to disrupt the VHL/HIF-1α interaction. J Am Chem Soc. 2012;134(10):4465–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Hagelkruys A, et al. The biology of HDAC in cancer: the nuclear and epigenetic components, in Histone Deacetylases: the Biology and Clinical Implication. In: Springer; 2011. p. 13–37.

    Google Scholar 

  44. Xu W, Parmigiani R, Marks P. Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene. 2007;26(37):5541.

    CAS  PubMed  Google Scholar 

  45. Carew JS, Giles FJ, Nawrocki ST. Histone deacetylase inhibitors: mechanisms of cell death and promise in combination cancer therapy. Cancer Lett. 2008;269(1):7–17.

    CAS  PubMed  Google Scholar 

  46. Andresen L, et al. Molecular regulation of MHC class I chain-related protein A expression after HDAC-inhibitor treatment of Jurkat T cells. J Immunol. 2007;179(12):8235–42.

    CAS  PubMed  Google Scholar 

  47. Shen L, Pili R. Class I histone deacetylase inhibition is a novel mechanism to target regulatory T cells in immunotherapy. Oncoimmunology. 2012;1(6):948–50.

    PubMed  PubMed Central  Google Scholar 

  48. Hull EE, Montgomery MR, Leyva KJ. HDAC inhibitors as epigenetic regulators of the immune system: impacts on cancer therapy and inflammatory diseases. BioMed Res Int. 2016;2016.

  49. Wang JC, Dick JE. Cancer stem cells: lessons from leukemia. Trends Cell Biol. 2005;15(9):494–501.

    CAS  PubMed  Google Scholar 

  50. Debeb BG, et al. Histone deacetylase inhibitor-induced cancer stem cells exhibit high pentose phosphate pathway metabolism. Oncotarget. 2016;7(19):28329.

    PubMed  PubMed Central  Google Scholar 

  51. Pantic I. Cancer stem cell hypotheses: impact on modern molecular physiology and pharmacology research. J Biosci. 2011;36(5):957–61.

    CAS  PubMed  Google Scholar 

  52. Rotili D, et al. Simplification of the tetracyclic SIRT1-selective inhibitor MC2141: coumarin-and pyrimidine-based SIRT1/2 inhibitors with different selectivity profile. Bioorg Med Chem. 2011;19(12):3659–68.

    CAS  PubMed  Google Scholar 

  53. Salek Farrokhi A, et al. Is it true that gut microbiota is considered as panacea in cancer therapy? J Cell Physiol. 2019.

  54. Burns MB, et al. Virulence genes are a signature of the microbiome in the colorectal tumor microenvironment. Genome Med. 2015;7(1):55.

    PubMed  PubMed Central  Google Scholar 

  55. Greiner T, Bäckhed F. Effects of the gut microbiota on obesity and glucose homeostasis. Trends Endocrinol Metab. 2011;22(4):117–23.

    CAS  PubMed  Google Scholar 

  56. Yousefi B, et al. Probiotics importance and their immunomodulatory properties. J Cell Physiol. 2019;234(6):8008–18.

    CAS  PubMed  Google Scholar 

  57. Aoyama M, Kotani J, Usami M. Butyrate and propionate induced activated or non-activated neutrophil apoptosis via HDAC inhibitor activity but without activating GPR-41/GPR-43 pathways. Nutrition. 2010;26(6):653–61.

    CAS  PubMed  Google Scholar 

  58. Meeran SM, Ahmed A, Tollefsbol TO. Epigenetic targets of bioactive dietary components for cancer prevention and therapy. Clin Epigenetics. 2010;1(3):101.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Meijer K, et al. Cell-based screening assay for anti-inflammatory activity of bioactive compounds. Food Chem. 2015;166:158–64.

    CAS  PubMed  Google Scholar 

  60. Ghasemian A, et al. Probiotics and their increasing importance in human health and infection control. Rev Med Microbiol. 2018;29(4):153–8.

    Google Scholar 

  61. Abel T, Zukin RS. Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders. Curr Opin Pharmacol. 2008;8(1):57–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Bourassa MW, et al. Butyrate, neuroepigenetics and the gut microbiome: can a high fiber diet improve brain health? Neurosci Lett. 2016;625:56–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Davie JR. Inhibition of histone deacetylase activity by butyrate. J Nutr. 2003;133(7):2485S–93S.

    CAS  PubMed  Google Scholar 

  64. Ali SR, et al. Impact of histone deacetylase inhibitors on microRNA expression and cancer therapy: a review. Drug Dev Res. 2015;76(6):296–317.

    CAS  PubMed  Google Scholar 

  65. Hamer HM, et al. The role of butyrate on colonic function. Aliment Pharmacol Ther. 2008;27(2):104–19.

    CAS  PubMed  Google Scholar 

  66. Mei S, Ho AD, Mahlknecht U. Role of histone deacetylase inhibitors in the treatment of cancer. Int J Oncol. 2004;25(6):1509–19.

    CAS  PubMed  Google Scholar 

  67. Bonci D, et al. The miR-15a–miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med. 2008;14(11):1271.

    CAS  PubMed  Google Scholar 

  68. Farazi TA, et al. MicroRNAs in human cancer, in MicroRNA cancer regulation. In: Springer; 2013. p. 1–20.

    Google Scholar 

  69. Li Y, Seto E. HDACs and HDAC inhibitors in cancer development and therapy. Cold Spring Harb Perspect Med. 2016;6(10):a026831.

    PubMed  PubMed Central  Google Scholar 

  70. Lauffer BE, et al. Histone deacetylase (HDAC) inhibitor kinetic rate constants correlate with cellular histone acetylation but not transcription and cell viability. J Biol Chem. 2013;288(37):26926–43.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Codd R, et al. Zn (II)-dependent histone deacetylase inhibitors: suberoylanilide hydroxamic acid and trichostatin A. Int J Biochem Cell Biol. 2009;41(4):736–9.

    CAS  PubMed  Google Scholar 

  72. Nalls D, et al. Targeting epigenetic regulation of miR-34a for treatment of pancreatic cancer by inhibition of pancreatic cancer stem cells. PloS one. 2011;6(8):e24099.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Mann BS, et al. FDA approval summary: vorinostat for treatment of advanced primary cutaneous T-cell lymphoma. Oncologist. 2007;12(10):1247–52.

    CAS  PubMed  Google Scholar 

  74. Beckers T, et al. Distinct pharmacological properties of second generation HDAC inhibitors with the benzamide or hydroxamate head group. Int J Cancer. 2007;121(5):1138–48.

    CAS  PubMed  Google Scholar 

  75. Zhao Z-N, et al. TSA suppresses miR-106b-93-25 cluster expression through downregulation of MYC and inhibits proliferation and induces apoptosis in human EMC. PLoS One. 2012;7(9):e45133.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Yousefi B, et al. Probiotics can really cure an autoimmune disease? Gene Rep. 2019:100364.

  77. Roller M, Rechkemmer G, Watzl B. Prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis modulates intestinal immune functions in rats. J Nutr. 2004;134(1):153–6.

    CAS  PubMed  Google Scholar 

  78. Meurman JH. Probiotics: do they have a role in oral medicine and dentistry? Eur J Oral Sci. 2005;113(3):188–96.

    PubMed  Google Scholar 

  79. Tuddenham S, Sears CL. The intestinal microbiome and health. Curr Opin Infect Dis. 2015;28(5):464.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Gholizadeh P, et al. Role of oral microbiome on oral cancers, a review. Biomed Pharmacother. 2016;84:552–8.

    CAS  PubMed  Google Scholar 

  81. Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nat Rev Immunol. 2016;16(6):341.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Lebeer S, Vanderleyden J, De Keersmaecker SC. Host interactions of probiotic bacterial surface molecules: comparison with commensals and pathogens. Nat Revi Microbiol. 2010;8(3):171.

    CAS  Google Scholar 

  83. Kumar M, et al. Cancer-preventing attributes of probiotics: an update. Int J Food Scie Nutr. 2010;61(5):473–96.

    CAS  Google Scholar 

  84. Pandey KR, Naik SR, Vakil BV. Probiotics, prebiotics and synbiotics-a review. J Food Sci Technol. 2015;52(12):7577–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  85. Chakraborti C. The status of synbiotics in colorectal cancer. Life Sci Med Res. 2011;2011:1–13.

    Google Scholar 

Download references

Acknowledgments

The authors thank Semnan University of Medical Sciences and Cancer Research Center of Semnan University of Medical Sciences.

Author information

Authors and Affiliations

Authors

Contributions

Amir Salek Farrokhi investigated and supervised the findings of this work, wrote the article, provided critical feedback, and helped the analysis of manuscript; Majid Eslami designed the study, helped supervise the project, and conceived the original idea, discussed the results, and commented on the manuscript; Bahman Yousefi contributed to the final version of the manuscript, supervised the project, and contributed to the interpretation of the results; Maryam Abdollahi developed the theoretical framework and processed the experimental data; Maryam Mohammadlou designed the model and the computational framework and analyzed the data.

Corresponding author

Correspondence to Majid Eslami.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Salek Farrokhi, A., Mohammadlou, M., Abdollahi, M. et al. Histone Deacetylase Modifications by Probiotics in Colorectal Cancer. J Gastrointest Canc 51, 754–764 (2020). https://doi.org/10.1007/s12029-019-00338-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12029-019-00338-2

Keywords

Navigation